Possible shortcomings of fertility study

In a much-publicized paper recently published in the journal
Fertility and Sterility, researchers at Loma Linda University
reported that high doses of a number of popular herbs had adverse
effects on hamster oocytes (eggs) and oocyte penetration by sperm
in an in vitro laboratory experiment [Ondrizek et al.,
1999]. Herbs tested were St. John's wort (Hypericum perforatum
L., Clusiaceae), echinacea (Echinacea purpurea L. [Moench],
Asteraceae), ginkgo (Ginkgo biloba L., Ginkgoaceae), and
saw palmetto (Serenoa repens [Bartr.] Small, Arecaceae).
All of the herbs except saw palmetto were reported to "damage
reproductive cells" at high concentrations.

Buried deep within the article is one sentence in which the
authors acknowledge the limitation of their research by suggesting,
"The possibility of a lack of physiologic effect in vivo
[in a living animal] should be considered." This type
of extremely preliminary testing is never considered conclusive
evidence, and if offered as evidence by supporters of herbal products,
would be considered "junk science." Nonetheless, the
journal Fertility and Sterility chose not only to publish
the study, but also to issue a press release bringing the exaggerated
results into the public spotlight. The resulting articles by The
New York Times and many other newspapers misled the public
into believing that a substantial adverse effect of the herbs
had been discovered through credible research.

In the study, saw palmetto, echinacea, ginkgo, and St. John's
wort extracts were tested in two concentrations to evaluate their
effects on hamster eggs stripped of the protective coating called
the zona pellucida. The hamster eggs were incubated with the herb
extracts for one hour and then tested to find out whether fertilization
would still occur. The results showed that saw palmetto had no
effect on fertilization and that a significant effect was seen
with St. John's wort, ginkgo, and echinacea only at high concentrations.
In addition, exposure to high concentrations of St. John's wort
and echinacea was reported to reduce sperm viability, and, in
the case of St. John's wort, to cause sperm mutation.

There are numerous problems with this type of testing. First,
in living animals, there is no evidence that the compounds in
the extracts used either enter the bloodstream or ever come in
contact with egg cells. Even if the extract were 100 percent absorbed
(which it is not) and if it remained unchanged by the liver (which
it does not), and if 100 percent of what was absorbed reached
the ovaries and the testes (which is unknown, but unlikely) the
"low concentration" is still too high by a factor of
six-fold. The researchers used a dilution of 1/1,000 of the standard
dose of each supplement, and suspended this amount in one milliliter
of medium. This is a simple and clear mathematical error. The
average blood volume of a human body is around 6,000 milliliters.
Hence the dilution should have been 1/6,000 of the dose instead
of 1/1,000.

Even if the researchers had used a correct dosage, they have
no way of knowing which parts of the body are reached by what
compounds in an extract. Many common substances will cause damage
to isolated cells in petri dishes. The elaborate digestive and
detoxification functions of the stomach, intestines, and liver
produce dramatic differences between what is consumed and what
eventually enters the bloodstream. The results of this test, namely
that this concentration of certain herb extracts reduced the fertilization
of hamster eggs, falls far short of the evidence necessary to
conclude there is any effect in living organisms, and is much
less than that required to put out a general caution to "infertile
couples" about the potential effects of the herbs in questions.

In conclusion, among many other possible study shortcomings,
the Loma Linda researchers appear to have miscalculated dosages
and used an inappropriate assay to reach sweeping, unsupportable
conclusions about the effects on fertility of several popular
herbal dietary supplements.